Interplay between steroid signalling and microRNAs: implications for hormone-dependent cancers

Abstract

Hormones are key drivers of cancer development. To date, interest has largely been focussed on the classical model of hormonal gene regulation, but there is increasing evidence for a role of hormone signalling pathways in post-translational regulation of gene expression. In particular, a complex and dynamic network of bi-directional interactions with microRNAs (miRs) at all stages of biogenesis and during target gene repression is emerging. miRs, which act mainly by negatively regulating gene expression through association with 3 0 -UTRs of mRNA species, are increasingly understood to be important in development, normal physiology and pathogenesis. Given recent demonstrations of altered miR profiles in a diverse range of cancers, their ability to function as oncogenes or tumour suppressors, and hormonal regulation of miRs, understanding mechanisms by which miRs are generated and regulated is vitally important. miRs are transcribed by RNA polymerase II and then processed in the nucleus by the Drosha-containing Microprocessor complex and in the cytoplasm by Dicer, before mature miRs are incorporated into the RNA-induced silencing complex. It is increasingly evident that multiple cellular signalling pathways converge upon the miR biogenesis cascade, adding further layers of regulatory complexity to modulate miR maturation. This review summarises recent advances in identification of novel components and regulators of the Microprocessor and Dicer complexes, with particular emphasis on the role of hormone signalling pathways in regulating their activity. Understanding hormone regulation of miR production and how this is perturbed in cancer are critical for the development of miR-based therapeutics and biomarkers.

miRNAs as novel biomarkers in the management of prostate cancer

“…Abnormal expression of miRNAs in cancer is related to different mechanisms, including genomic mutations, epigenetic changes, chromosomal abnormalities and alterations in miRNA biogenesis, i.e. the altered expression of the miRNA processing endoribonuclease Dicer [20].…”

MicroRNA: sex steroids, hormonal carcinogenesis, hormonal sensitivity of tumor tissue

“…Накопление данных о биологических функциях некодирующих РНК, в частности так называемых микроРНК (microRNA, miRNA), подготовило почву для исследования воз-можного влияния этой группы регуляторных молекул на внутриклеточные эффекты ПГ. Согласно результа-там недавних исследований, взаимозависимые иска-жения регуляторных функций ПГ и профиля микроРНК играют значимую патогенетическую роль в развитии РМЖ и РПЖ [5][6][7].…”

“…С учетом роли экзо-сомальной микроРНК в процессе опухолевой диссе-минации [38], андроген-регулируемые сдвиги профи-ля экспрессии микроРНК клетками РПЖ могут иметь значение в процессе формирования отдаленных мета-стазов [39]. Углубленная оценка функциональной взаимосвя-зи андрогенов и микроРНК в клетках РПЖ дана в об-зорной статье C. E. Fletcher et al [5], где приведен пе-речень 13 микроРНК, андроген-зависимость которых была показана в двух и более независимых исследова-ниях. С учетом общего количества известных микро-РНК, относительно малое число достоверно вовлечен-ных в обсуждаемый процесс молекул говорит о том, что стимуляция AR в клетках РПЖ вызывает весьма характерные изменения микроРНК-профиля.…”

Therapeutic Applications of Vegf Inhibitors in Breast Cancer.

“…miR-based therapeutic approaches include inhibition of oncomiRs by antisense oligonucleotides, restoration of tumour suppressors using miR mimics, and chemical modification of miRs (6).The lnRNAs HOTAIR, SPRY4-IT1, GAS5, and PANDAR, new players in tumour development and prognosis may have theranostic applications in breast cancer (7). Long non-coding RNAs (lncRNAs) exert most of their functions through protein interactions.…”